NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008] See more...

Aliases for NPAS4 Gene

Aliases for NPAS4 Gene

  • Neuronal PAS Domain Protein 4 2 3 5
  • BHLHe79 2 3 4
  • PASD10 2 3 4
  • NXF 2 3 4
  • Class E Basic Helix-Loop-Helix Protein 79 3 4
  • Neuronal PAS Domain-Containing Protein 4 3 4
  • HLH-PAS Transcription Factor NXF 3 4
  • PAS Domain-Containing Protein 10 3 4
  • Neuronal PAS4 3 4
  • Le-PAS 2 3
  • BHLHE79 4
  • NPAS4 5

External Ids for NPAS4 Gene

Previous GeneCards Identifiers for NPAS4 Gene

  • GC11P065946
  • GC11P066188
  • GC11P062516
  • GC11P066421
  • GC11P066467
  • GC11P066487

Summaries for NPAS4 Gene

Entrez Gene Summary for NPAS4 Gene

  • NXF is a member of the basic helix-loop-helix-PER (MIM 602260)-ARNT (MIM 126110)-SIM (see SIM2; MIM 600892) (bHLH-PAS) class of transcriptional regulators, which are involved in a wide range of physiologic and developmental events (Ooe et al., 2004 [PubMed 14701734]).[supplied by OMIM, Mar 2008]

GeneCards Summary for NPAS4 Gene

NPAS4 (Neuronal PAS Domain Protein 4) is a Protein Coding gene. Diseases associated with NPAS4 include Kagami-Ogata Syndrome and Disease Of Mental Health. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is EPAS1.

UniProtKB/Swiss-Prot Summary for NPAS4 Gene

  • Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hyppocampus (By similarity). Plays a key role in the structural and functional plasticity of neurons (By similarity). Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (By similarity). In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (By similarity). In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (By similarity). The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (By similarity). Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (By similarity). Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734). Can activate the CME (CNS midline enhancer) element (PubMed:14701734).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NPAS4 Gene

Genomics for NPAS4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NPAS4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J066408 Promoter/Enhancer 1.8 Ensembl ENCODE CraniofacialAtlas 250.7 +0.8 834 2.9 BCLAF1 SP1 ZNF654 MYC ZNF592 ZNF223 POLR2A ZBTB10 NONO CTCF ENSG00000254510 NPAS4 RIN1 ACTN3 ENSG00000201733 SLC29A2 MRPL11 PELI3 DPP3 DPP3-DT
GH11J066420 Promoter 0.6 EPDnew 250.4 +12.1 12094 0.1 ZBTB21 ZNF629 POLR2A EZH2 HSALNG0085022 NPAS4 ENSG00000254510 PELI3
GH11J065884 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 10.1 -514.5 -514482 20.5 BCLAF1 SP1 ZNF207 NCOR1 MYC ZNF654 ZNF600 IKZF1 SIX5 SSRP1 FOSL1 FIBP DRAP1 HSALNG0084963 RBM14 KAT5 SNX32 RBM4 MUS81 ENSG00000254461
GH11J065833 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 10.1 -574.9 -574922 2.4 SP1 ZNF207 POLR2A CTCF PLRG1 FOXA1 SIN3A MBD2 NR2C1 MCM3 SNX32 HSALNG0084951 MRPL11 ZFPL1 ENSG00000254855 EIF1AD RBM4B BBS1 NAALADL1 POLA2
GH11J066694 Enhancer 1.2 Ensembl ENCODE 9.9 +286.0 285953 1.1 BCLAF1 ZNF600 MYC ZNF654 IKZF1 SSRP1 ZNF580 ZNF592 CEBPA BRCA1 piR-40773 SPTBN2 C11orf80 RCE1 ZDHHC24 ACTN3 LRFN4 PC RNU7-23P RNU1-84P
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NPAS4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NPAS4

Top Transcription factor binding sites by QIAGEN in the NPAS4 gene promoter:
  • Elk-1
  • FOXD3
  • MAZR
  • MIF-1
  • MyoD
  • NRSF form 1
  • NRSF form 2
  • Olf-1
  • SEF-1 (1)
  • STAT3

Genomic Locations for NPAS4 Gene

Latest Assembly
chr11:66,408,922-66,426,707
(GRCh38/hg38)
Size:
17,786 bases
Orientation:
Plus strand

Previous Assembly
chr11:66,188,475-66,194,178
(GRCh37/hg19 by Entrez Gene)
Size:
5,704 bases
Orientation:
Plus strand

chr11:66,188,475-66,194,178
(GRCh37/hg19 by Ensembl)
Size:
5,704 bases
Orientation:
Plus strand

Genomic View for NPAS4 Gene

Genes around NPAS4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NPAS4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NPAS4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NPAS4 Gene

Proteins for NPAS4 Gene

  • Protein details for NPAS4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IUM7-NPAS4_HUMAN
    Recommended name:
    Neuronal PAS domain-containing protein 4
    Protein Accession:
    Q8IUM7
    Secondary Accessions:
    • B7ZL81
    • Q8N8S5
    • Q8N9Q9

    Protein attributes for NPAS4 Gene

    Size:
    802 amino acids
    Molecular mass:
    87117 Da
    Quaternary structure:
    • Efficient DNA binding requires dimerization with another bHLH protein (PubMed:14701734, PubMed:24465693). Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:24465693).
    SequenceCaution:
    • Sequence=BAC04271.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for NPAS4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NPAS4 Gene

Post-translational modifications for NPAS4 Gene

Other Protein References for NPAS4 Gene

Antibodies for research

  • Abcam antibodies for NPAS4
  • Santa Cruz Biotechnology (SCBT) Antibodies for NPAS4

No data available for DME Specific Peptides for NPAS4 Gene

Domains & Families for NPAS4 Gene

Gene Families for NPAS4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NPAS4 Gene

InterPro:
Blocks:
  • PAS domain
  • PAS fold-3

Suggested Antigen Peptide Sequences for NPAS4 Gene

GenScript: Design optimal peptide antigens:
  • PAS domain-containing protein 10 (NPAS4_HUMAN)
genes like me logo Genes that share domains with NPAS4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for NPAS4 Gene

Function for NPAS4 Gene

Molecular function for NPAS4 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hyppocampus (By similarity). Plays a key role in the structural and functional plasticity of neurons (By similarity). Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (By similarity). In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (By similarity). In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (By similarity). The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (By similarity). Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (By similarity). Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734). Can activate the CME (CNS midline enhancer) element (PubMed:14701734).

Phenotypes From GWAS Catalog for NPAS4 Gene

Gene Ontology (GO) - Molecular Function for NPAS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IBA 21873635
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 14701734
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific IDA,ISA --
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 14701734
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with NPAS4: view
genes like me logo Genes that share phenotypes with NPAS4: view

Animal Models for NPAS4 Gene

MGI Knock Outs for NPAS4:

miRNA for NPAS4 Gene

miRTarBase miRNAs that target NPAS4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPAS4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NPAS4 Gene

Localization for NPAS4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NPAS4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NPAS4 gene
Compartment Confidence
nucleus 4
mitochondrion 2
cytosol 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1

Gene Ontology (GO) - Cellular Components for NPAS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA --
GO:0005667 transcription factor complex IEA --
GO:0098794 postsynapse IEA --
genes like me logo Genes that share ontologies with NPAS4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NPAS4 Gene

Pathways & Interactions for NPAS4 Gene

PathCards logo

SuperPathways for NPAS4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for NPAS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0007399 nervous system development IEA --
GO:0007612 learning ISS --
GO:0007614 short-term memory ISS --
GO:0007616 long-term memory ISS --
genes like me logo Genes that share ontologies with NPAS4: view

No data available for Pathways by source and SIGNOR curated interactions for NPAS4 Gene

Drugs & Compounds for NPAS4 Gene

No Compound Related Data Available

Transcripts for NPAS4 Gene

mRNA/cDNA for NPAS4 Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NPAS4

Alternative Splicing Database (ASD) splice patterns (SP) for NPAS4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8
SP1:
SP2: -

Relevant External Links for NPAS4 Gene

GeneLoc Exon Structure for
NPAS4

Expression for NPAS4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NPAS4 Gene

mRNA differential expression in normal tissues according to GTEx for NPAS4 Gene

This gene is overexpressed in Brain - Cerebellum (x13.1), Brain - Cerebellar Hemisphere (x10.9), and Pituitary (x6.5).

Protein differential expression in normal tissues from HIPED for NPAS4 Gene

This gene is overexpressed in Brain (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for NPAS4 Gene



Protein tissue co-expression partners for NPAS4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NPAS4

SOURCE GeneReport for Unigene cluster for NPAS4 Gene:

Hs.256036

mRNA Expression by UniProt/SwissProt for NPAS4 Gene:

Q8IUM7-NPAS4_HUMAN
Tissue specificity: Brain.

Evidence on tissue expression from TISSUES for NPAS4 Gene

  • Nervous system(4.5)
genes like me logo Genes that share expression patterns with NPAS4: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for NPAS4 Gene

Orthologs for NPAS4 Gene

This gene was present in the common ancestor of animals.

Orthologs for NPAS4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NPAS4 29 30
  • 99.88 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NPAS4 29 30
  • 92.46 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NPAS4 29 30
  • 91.71 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Npas4 29 16 30
  • 90.25 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Npas4 29
  • 90.21 (n)
Oppossum
(Monodelphis domestica)
Mammalia NPAS4 30
  • 79 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LOC101750093 29
  • 53.43 (n)
Lizard
(Anolis carolinensis)
Reptilia NPAS4 30
  • 34 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia npas4 29
  • 55.71 (n)
Zebrafish
(Danio rerio)
Actinopterygii npas4a 29 30
  • 59.53 (n)
OneToMany
NPAS4 (2 of 3) 30
  • 46 (a)
OneToMany
npas4b 30
  • 38 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta dys 30
  • 19 (a)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea cky-1 30
  • 24 (a)
OneToOne
Species where no ortholog for NPAS4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NPAS4 Gene

ENSEMBL:
Gene Tree for NPAS4 (if available)
TreeFam:
Gene Tree for NPAS4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NPAS4: view image
Alliance of Genome Resources:
Additional Orthologs for NPAS4

Paralogs for NPAS4 Gene

Paralogs for NPAS4 Gene

(1) SIMAP similar genes for NPAS4 Gene using alignment to 2 proteins:

  • NPAS4_HUMAN
  • B7ZL81_HUMAN
genes like me logo Genes that share paralogs with NPAS4: view

Variants for NPAS4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NPAS4 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs138708121 Benign: not provided 66,424,369(+) G/C
NM_178864.4(NPAS4):c.1479G>C (p.Ser493=)
SYNONYMOUS
rs144132334 Benign: not provided 66,425,062(+) G/A
NM_178864.4(NPAS4):c.2172G>A (p.Glu724=)
SYNONYMOUS
rs147463475 Likely Benign: not provided 66,424,994(+) A/Gp.Asn702Asp
NM_178864.4(NPAS4):c.2104A>G (p.Asn702Asp)
MISSENSE
rs71457718 Benign: not provided 66,424,388(+) C/Ap.Gln500Lys
NM_178864.4(NPAS4):c.1498C>A (p.Gln500Lys)
MISSENSE
rs77039322 Benign: not provided 66,425,209(+) T/C
NM_178864.4(NPAS4):c.2319T>C (p.Tyr773=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for NPAS4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for NPAS4 Gene

Variant ID Type Subtype PubMed ID
nsv832193 CNV loss 17160897

Variation tolerance for NPAS4 Gene

Residual Variation Intolerance Score: 5.28% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.67; 31.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NPAS4 Gene

Human Gene Mutation Database (HGMD)
NPAS4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NPAS4
Leiden Open Variation Database (LOVD)
NPAS4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NPAS4 Gene

Disorders for NPAS4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for NPAS4 Gene - From: COP

Disorder Aliases PubMed IDs
kagami-ogata syndrome
  • uniparental disomy, paternal, chromosome 14
disease of mental health
  • mental health
- elite association - COSMIC cancer census association via MalaCards
Search NPAS4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NPAS4

genes like me logo Genes that share disorders with NPAS4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NPAS4 Gene

Publications for NPAS4 Gene

  1. Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator drebrin gene expression. (PMID: 14701734) Ooe N … Kaneko H (Molecular and cellular biology 2004) 2 3 4
  2. Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function. (PMID: 24465693) Bersten DC … Whitelaw ML (PloS one 2014) 3 4
  3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. (PMID: 30021884) Fasci D … Heck AJR (Molecular & cellular proteomics : MCP 2018) 3

Products for NPAS4 Gene

Sources for NPAS4 Gene